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Biomedical subjects

R Rosenthal

Publications and source records attributed to R Rosenthal.

At least 37 records · Page 2Linked to original sources

Fibroblast growth factor receptor 2 (FGFR2) in brain neurons and retinal pigment epithelial cells act via stimulation of neuroendocrine L-type channels (Ca(v)1.3).

In contrast to the fibroblast growth factor receptor 1 (FGFR1), little is known about intracellular signaling of FGFR2. The signaling cascade of FGFR2 was studied using the perforated patch configuration of the patch-clamp technique in cultured rat retinal pigment epithelial (RPE) cells that express both FGFR1 and FGFR2. Interaction of signaling proteins was studied using immunoprecipitation techniques with membrane proteins from RPE cells and freshly isolated rat brain. When Ba(2+) currents through L-type channels were studied, extracellular application of bFGF (10 ng/ml) led to a shift of the steady-state activation to more negative values. In 50% of cells, an additional increase in maximal current amplitude was observed. This effect was blocked by the tyrosine kinase inhibitor lavendustin A (10(-5) M) but was not influenced by the FGFR1 blocker SU5402 (2 x 10(-5) M) or by the blocker for src-kinase herbimycin A (10(-5) M). Immunoprecipitation of FGFR2 led to coprecipitation of alpha 1D Ca(2+) channel subunits and precipitation of alpha 1D subunits led to coprecipitation of FGFR2. Immunoprecipitation of FGFR1 did not result in the coprecipitation with alpha 1D Ca(2+) channel subunits. The coprecipitation results were comparable when using brain tissue and RPE cells. The alpha 1D subunit-specific band were stained with antiphosphotyrosine antibodies. We conclude that FGFR2 acts via a different signaling cascade than FGFR1. This cascade involves an src-kinase-independent, close functional interaction of FGFR2 and the alpha subunit of neuroendocrine L-type channels.

Animals↗

Meta-analysis: recent developments in quantitative methods for literature reviews.

We describe the history and current status of the meta-analytic enterprise. The advantages and historical criticisms of meta-analysis are described, as are the basic steps in a meta-analysis and the role of effect sizes as chief coins of the meta-analytic realm. Advantages of the meta-analytic procedures include seeing the "landscape" of a research domain, keeping statistical significance in perspective, minimizing wasted data, becoming intimate with the data summarized, asking focused research questions, and finding moderator variables. Much of the criticism of meta-analysis has been based on simple misunderstanding of how meta-analyses are actually carried out. Criticisms of meta-analysis that are applicable are equally applicable to traditional, nonquantitative, narrative reviews of the literature. Much of the remainder of the chapter deals with the processes of effect size estimation, the understanding of the heterogeneity of the obtained effect sizes, and the practical and scientific importance of the effect sizes obtained.

Humans↗

[Pheochromocytoma: diagnosis and treatment].

Phaeochromocytoma is a rare tumour which produces a variety of symptoms. The most important factor is to think of the diagnosis, and there are many biochemical and pharmacological tests as well as radiological procedures to confirm it. Once the phaeochromocytoma is localised, it should, if possible, be removed. Surgery is the treatment of choice. In 1972 Ross described the diagnosis and therapy as "think of it, confirm it, find it and remove it". Today, 28 years later, this paper reviews the diagnosis and therapy of phaeochromocytoma under these key headings.

Adrenal Gland Neoplasms↗

Activation of neuroendocrine L-type channels (alpha1D subunits) in retinal pigment epithelial cells and brain neurons by pp60(c-src).

The aim of this study is to characterize the subtype of tyrosine kinase-regulated L-type Ca(2+) channels in retinal pigment epithelial (RPE) cells. Ca(2+) channel alpha1D-subunits were enriched by immunoprecipitation from membrane proteins isolated from rat RPE cells. Western blot analysis of the precipitates revealed coprecipitation of pp60(c-src). In addition, in precipitates obtained with antibodies against pp60(c-src), alpha1D-subunits were identified. The same was observed in immunoprecipitations from rat brain neurons. Tyrosine phosphorylation of alpha1D-subunits was confirmed using anti-phosphotyrosine antibodies. Ba(2+) currents through L-type channels in cultured rat RPE cells were increased by intracellular application of active pp60(c-src) (30 U/ml) (heat-inactivated pp60(c-src) had no effect). Thus, L-type channels of the neuroendocrine subtype can be expressed in epithelial cells and are activated by tyrosine kinase of the src subtype. This kind of regulation is also suggested for brain-derived neurons.

Animals↗

Contrasts and correlations in effect-size estimation.

This article describes procedures for presenting standardized measures of effect size when contrasts are used to ask focused questions of data. The simplest contrasts consist of comparisons of two samples (e.g., based on the independent t statistic). Useful effect-size indices in this situation are members of the g family (e.g., Hedges's g and Cohen's d) and the Pearson r. We review expressions for calculating these measures and for transforming them back and forth, and describe how to adjust formulas for obtaining g or d from t, or r from g, when the sample sizes are unequal. The real-life implications of d or g calculated from t become problematic when there are more than two groups, but the correlational approach is adaptable and interpretable, although more complex than in the case of two groups. We describe a family of four conceptually related correlation indices: the alerting correlation, the contrast correlation, the effect-size correlation, and the BESD (binomial effect-size display) correlation. These last three correlations are identical in the simple setting of only two groups, but differ when there are more than two groups.

Analysis of Variance↗

Neuroprotective antioxidants from marijuana.

Cannabidiol and other cannabinoids were examined as neuroprotectants in rat cortical neuron cultures exposed to toxic levels of the neurotransmitter, glutamate. The psychotropic cannabinoid receptor agonist delta 9-tetrahydrocannabinol (THC) and cannabidiol, (a non-psychoactive constituent of marijuana), both reduced NMDA, AMPA and kainate receptor mediated neurotoxicities. Neuroprotection was not affected by cannabinoid receptor antagonist, indicating a (cannabinoid) receptor-independent mechanism of action. Glutamate toxicity can be reduced by antioxidants. Using cyclic voltametry and a fenton reaction based system, it was demonstrated that Cannabidiol, THC and other cannabinoids are potent antioxidants. As evidence that cannabinoids can act as an antioxidants in neuronal cultures, cannabidiol was demonstrated to reduce hydroperoxide toxicity in neurons. In a head to head trial of the abilities of various antioxidants to prevent glutamate toxicity, cannabidiol was superior to both alpha-tocopherol and ascorbate in protective capacity. Recent preliminary studies in a rat model of focal cerebral ischemia suggest that cannabidiol may be at least as effective in vivo as seen in these in vitro studies.

Animals↗

[Variants of atrial myxoma].

We describe two different manifestations of cardiac myxoma. Both have in common late diagnosis. The first patient suffered from a right sided myxoma. The histological diagnosis is unexpected. In the second case, the diagnosis of a myxoma in the left arterial cavity is made only two years after the first symptoms. We discuss epidemiology, symptoms, diagnosis, treatment and prognosis of atrial myxoma.

Aged↗

Determination of blood flow in the finger using near-infrared spectroscopy.

Wavelengths in the near-infrared range have much better penetrance in organic substances than visible light. We used near-infrared spectroscopy to determine non-invasively blood flow in the fingertip. We used laser Doppler technology to measure skin blood flow as a comparison procedure. We performed several manoeuvres to change blood flow. These included restriction of flow, thermal stimulation and post-occlusion hyperaemia. Near-infrared measurements had coefficients of variation of 10-15% at the various wavelengths, contrasting with variability of 30-40% with laser Doppler measurement. With restriction of blood flow, there was a downward shift in the absorbance curve. With thermal stimulation and with post-occlusion hyperaemia, there was a rise in the curve. The flow-induced shifts in the absorbance curve were particularly pronounced in the range of 850-970 nm. The correlation between absorbance values and laser Doppler-determined blood flow was also highest in this range, averaging about 0.69 (n = 625). Near-infrared spectroscopy can therefore be used to scan the fingertip. The absorbances obtained do reflect changes in blood flow. There is a correlation with skin blood flow, although near-infrared measurements are affected by blood flow in the full breadth of the finger, not just the skin. We can measure this blood flow with significant reproducibility. It may be possible to use near-infrared spectroscopy to measure the concentration of individual blood components.

Fingers↗

Negative symptoms in stroke patients and length of hospital stay.

The purpose of this study was to assess whether the presence and severity of psychiatric symptoms in stroke patients correlate with their length of stay (LOS) in a rehabilitation unit, with special emphasis on the role of negative symptoms (NS). Twenty-three stroke patients, consecutively recruited from the inpatient rehabilitation unit, were evaluated on admission with the Mini-Mental State Examination (MMSE), the Positive and Negative Symptom Scale (PANSS), the Hamilton Depression Rating Scale (HDRS), the Scale for Assessment of Negative Symptoms (SANS), and the Functional Independent Measure (FIM). NS scores significantly correlated with LOS, with SANS total score being the most informative, and the attentional impairment subscale the least. The group of patients with pronounced NS stayed in the hospital twice as long as patients with the score on the NS subscale of PANSS below 16. These two groups did not differ in their cognitive performance or in the positive symptom subscale of PANSS scores. Total FIM score on admission was lower and HDRS scores higher in patients with pronounced NS. However, these differences, unlike those of LOS, have not reached statistical significance. The presence and severity of NS in stroke patients are associated with a longer hospital stay. Identification and treatment of NS might lead to a faster discharge from rehabilitation unit.

Aged↗

Methylphenidate treatment of negative symptoms in patients with dementia.

This pilot study evaluated response of negative symptoms (NS) to methylphenidate in patients with dementia and relationships between NS, depression, and cognitive deficits in these patients. Consecutively admitted patients with NS and dementia--12 with dementia of Alzheimer's type and 15 with vascular dementia--were rated on severity of NS (SANS and PANSS-N scales), depressive symptoms (Ham-D), and cognitive impairment (MMSE) before and after treatment with methylphenidate. NS decreased significantly, and cognitive scores increased. A decrease in depression scores was nonsignificant after all variance attributable to NS was removed. NS, depression, and cognitive scores were not significantly intercorrelated. Results were similar for Alzheimer's and vascular dementia patients. Negative symptoms in dementia patients appear responsive to methylphenidate treatment. This effect may underlie putative changes in symptoms of depression observed by other researchers.

Aged↗

Treatment of hypercholesterolemia in the Watanabe rabbit using allogeneic hepatocellular transplantation under a regeneration stimulus.

Numerous studies have reported successful allotransplantation of hepatocytes. However, none have shown long-term correction of a liver-related metabolic defect. In this study, we used a method of regional hepatocyte transplantation and subsequent induction of transplanted cell proliferation by regeneration response in the transplant-bearing liver lobes. New Zealand White rabbits were used as cell donors and Watanabe heritable hyperlipidemic (WHHL) rabbits were used as cell recipients (2 x 10(8) cells/rabbit). All recipient rabbits were maintained on daily cyclosporine. Two weeks after baseline serum cholesterol determination, group I WHHL rabbits (n = 7) received an infusion of cells into the right lateral liver lobe, and a loose ligature was placed around the portal venous branch supplying the anterior lobe. After 1 week, to allow engraftment, the portal venous branch was ligated, which resulted in the atrophy of the affected liver parenchyma and induction of hyperplasia in the transplant-bearing liver tissue. Group II rabbits (n = 6) were transplanted with New Zealand White hepatocytes without portal branch ligation (PBL) and group III rabbits (n = 4) were subjected to sham transplantation (saline) and PBL. The experimental period extended to 150 days after transplantation. All WHHL rabbits transplanted with normal hepatocytes showed reduction in serum cholesterol and low-density lipoprotein (LDL) levels. Group I (PBL-stimulated) recipients demonstrated a more pronounced and sustained effect than group II animals (P < 0.05). Group III controls showed only a slight, typical for aging decrease in serum cholesterol. Group I recipient livers perfused with LDL labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethyl indocarbocyanine perchlorate (DiI) showed much higher numbers of DiI-LDL-positive hepatocytes than those of group II recipients. In conclusion, a liver regeneration stimulus enhanced the population of transplanted hepatocytes and their functional effect in a large animal model of inborn error of liver metabolism.

Alanine Transaminase↗

One hundred consecutive laparoscopic cholangiograms. Results and conclusions.

BACKGROUND: In 100 consecutive patients who underwent laparoscopic cholecystectomy, the feasibility, reliability, and cost of routine laparoscopic cholangiography were prospectively studied. METHODS: Fluoroscopic cholangiograms with multiple exposures were successfully completed in all patients in an average time of 6.9 min. RESULTS: Twenty-one percent were abnormal, and 15 common duct stones and 6 significant anatomic anomalies detected. Thirteen out of 15 patients with common duct stones had preoperative suspicion of common duct stones. Two out of 15 were completely unsuspected. The average cost of cholangiography was $768, and there were no complications related to the procedure. There were no false interpretations. CONCLUSIONS: When compared with selective preoperative endoscopic retrograde cholangiopancreatography (ERCP), routine laparoscopic cholangiography is safer, more accurate, and less costly, and may have the added benefit of potentially reducing iatrogenic injuries in patients with anatomic variations. Routine laparoscopic cholangiography should be considered by all surgeons.

Adult↗

Laparoscopic colectomy vs traditional colectomy for diverticulitis. Outcome and costs.

BACKGROUND: The aim of this study was to evaluate the outcome of patients undergoing laparoscopic colectomy for diverticulitis. METHODS: Fourteen consecutive patients undergoing laparoscopic sigmoid colectomy (LSC) for diverticulitis were evaluated. Medical records from a control group of 14 matched patients undergoing traditional open sigmoid colectomy (OSC) for diverticulitis were reviewed for comparison. RESULTS: Mean age, operative time, morbidity, and mortality of the LSC and OSC groups were not significantly different. However, the mean estimated blood loss (171cc vs 321cc), days to p.o. liquids (2.9 vs 6.1), and postoperative stay (6.3 vs 9.2 days) were all significantly less in the LSC patients. Although the mean operating room charges were greater in the LSC patients ($10,589 vs $8,207) the mean total hospital charges ($29,981 vs $36,745) and costs ($11,528 vs $13,426) were markedly less. CONCLUSIONS: Compared with OSC for diverticulitis, LSC results in a more rapid return of bowel function and shortened hospital stay. Despite the greater operating room charges of LSC, the total hospital charges and costs are lessened.

Adult↗

Detecting anxiety and defensiveness from visual and auditory cues.

Defensive individuals have been shown to differ from nondefensive individuals on a number of physiological and behavioral measures. We report two studies on observers' inferences of defensiveness, and the contribution of communication channels in the inference of defensiveness. Observers judged high and low state anxious segments of high and low trait anxious defensive and nondefensive individuals. Accurate assessments were made of (a) defensiveness, (b) state anxiety, and (c) trait anxiety: Individuals with higher levels of each variable were perceived as more anxious compared with the lower level. Effects for defensiveness and state anxiety were greater in audio-only segments, while effects for trait anxiety were greater in video-only segments. Inferences of defensiveness were greater at higher levels of state anxiety and trait anxiety. Low trait anxious defensive individuals were perceived as more anxious than the true low trait anxious. Results for defensiveness and trait anxiety were replicated in Study 2, and observers' perceptions of state anxiety matched individuals' self-reports: Defensive individuals with maximal differences between high and low state anxiety were seen as more anxious in high state anxiety, while defensive individuals with minimal differences between high and low state anxiety were regarded as less anxious in high state anxiety.

Adult↗

Cost-effective management of complicated choledocholithiasis: laparoscopic transcystic duct exploration or endoscopic sphincterotomy.

BACKGROUND: In the United States of America, approximately 700,000 patients undergo laparoscopic cholecystectomy (LC) each year and at least 10 percent of these patients will have common bile duct stones (CBDS). The purpose of this study was to evaluate patients with choledocholithiasis and compare the economic and clinical results obtained by LC with endoscopic sphincterotomy (ES) with those of LC with laparoscopic transcystic common bile duct exploration (LTCBDE). STUDY DESIGN: From June 1991 to September 1994 patients undergoing LC plus LTCBDE and those undergoing LC plus ES at a single institution were compared where cost data were available. Of the 76 patients with choledocholithiasis, 59 patients underwent LC plus LTCBDE (group 1) and 17 patients underwent LC plus ES (group 2). A subset of group 1 patients undergoing urgent LC plus LTCBDE (group 3) for cholecystitis, cholangitis, or pancreatitis plus laparoscopy were examined separately. RESULTS: Laparoscopic cholecystectomy plus LTCBDE, whether including all-comers (group 1) or just urgent cases (group 3), was associated with a significantly decreased length of hospital stay (6.1 and 6.9 days, respectively, compared with group 2, 12.4 days) (p < 0.001). The morbidity of patients in group 1 was also markedly lower than for patients in group 2; 12 percent compared with 41 percent, respectively. Patients in group 1 had a significantly decreased cost of hospitalization (+13,151), when compared with patients in group 2 (+18,712) (p = 0.05). This difference is even more pronounced when professional fee reimbursement is considered. The cost of treatment for patients in group 1 was +14,732 compared with +21,125 for patients in group 2 (p < 0.05). The total hospital cost for patients in group 3 was only +13,564 compared with +18,712 for patients in group 2. When professional reimbursement was considered, the cost was +15,150 for patients in group 3 compared with +21,125 for patients in group 2. CONCLUSIONS: Patients undergoing LC plus LTCBDE for CBDS, whether urgently or electively, have markedly decreased morbidity rates, length of hospital stay, and costs when compared with patients undergoing LC plus ES.

California↗

Update on transcystic exploration of the bile duct.

Selective use of transcystic bile duct exploration during laparoscopic cholecystectomy is a safe and highly effective approach for treatment of most common duct stones. The technique obviates the need for selective endoscopic retrograde cholangiopancreatography-sphincterotomy prior to cholecystectomy and is a more cost-effective approach.

Cholangiopancreatography, Endoscopic Retrograde↗